Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity.
Bottom Line: Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization.Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell-intrinsic block in plasma cell differentiation.Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.
Affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.Show MeSH
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Mentions: In the light of the emerging importance of the cytoskeleton in regulating B cell functions, we sought to characterize the role of the RhoGTPase Cdc42 during B cell development and activation in vivo. To do this, conditionally targeted Cdc42flox/flox mice were crossed with mice expressing Cre recombinase under the promoter of the mb1 gene (Fig. 1 A; Wu et al., 2006; Hobeika et al., 2006). As mb1 encodes the Igα subunit of the BCR, this approach circumvents limitations associated with gene targeting through the Cd19 locus, which is known in some cases to lead to incomplete deletion, especially in the early B cell lineage (Rickert et al., 1997). Indeed, we observed that although Cdc42 was highly expressed early during B cell development in WT controls, expression was completely abrogated in Cdc42flox/floxmb1Cre+/− mice (hereafter designated Cdc42 KO; Fig. 1 D).
Affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.